Dopamine inhibits renal Na+: HCO3- cotransporter in rabbits and normotensive rats but not in spontaneously hypertensive rats

Background Dopamine (DA) is thought to regulate renal proximal transport th rough the inhibition of the Na+K+-ATPase and/or Na+/H+ exchanger. Defects i n this dopaminergic system are proposed to be a pathogenic factor of geneti c hypertension. However, microperfusion studies have not consistently confi rmed direct tubular effects of DA. Methods. Isolated proximal straight tubules were perfused peritubularly wit h Dulbecco's modified Eagle's tissue culture medium (DMEM) containing norep inephrine (NE) to improve incubation conditions. Intracellular Na+ concentr ations ([Na+](i)) and cell pH (pH(i)) were measured with fluorescence probe s. Results. When incubated in DMEM plus NE, DA increased [Na+](i) in rabbit tu bules. Inhibition of Na+,K+-ATPase could not explain this response, as it w as not suppressed by ouabain. An analysis of pH(i) responses to bath HCO3- reduction revealed that DA, SKF 38393 (a DA(1) agonist), and adenosine 3',5 '-cyclic monophosphate (cAMP) inhibited the basolateral Na+:HCO; cotranspor ter in rabbit and Wistar-Kyoto rat (WKY), if its transport stoichiometry wa s converted to 3 HCO3- :1 Na+ by DMEM plus NE incubation. The inhibitory ef fect of DA was abolished by SCH: 23390, a DA(1) antagonist, but not by (-)- sulpiride, a DA(2) antagonist. In spontaneously hypertensive rats (SHRs), h owever, DA and SKF 38393 failed to inhibit the cotransporter, although the inhibitory effects of cAMP and parathyroid hormone were comparable to those in WKY. Conclusion. These results indicate that DA inhibits the Na+:HCO3- cotranspo rter in renal proximal tubules and also suggest that dysregulation of the c otransporter possibly through the defect in DA, receptor signaling, could p lay an important role in development of hypertension in SHRs.